Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial.

Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Investigative ophthalmology & visual science (Impact Factor: 3.43). 12/2010; 51(12):6131-9. DOI: 10.1167/iovs.10-5637
Source: PubMed

ABSTRACT To investigate the safety and preliminary efficacy of OT-551, a disubstituted hydroxylamine with antioxidant properties, for the treatment of geographic atrophy (GA), the advanced atrophic form of age-related macular degeneration (AMD).
The study was a single-center, open-label phase II trial, enrolling 10 participants with bilateral GA. Topical 0.45% OT-551 was administered in one randomly assigned eye three times daily for 2 years. Safety measures were assessed by complete ophthalmic examination, fundus photography, and review of symptoms. The primary efficacy outcome measure was the change in best corrected visual acuity at 24 months. Secondary efficacy measures included changes in area of GA, contrast sensitivity, microperimetry measurements, and total drusen area from baseline.
Study drug was well tolerated and was associated with few adverse events. The mean change in BCVA at 2 years was +0.2 ± 13.3 letters in the study eyes and -11.3 ± 7.6 letters in fellow eyes (P = 0.0259). However, no statistically significant differences were found between the study and fellow eyes for all other secondary outcome measures.
OT-551 was well tolerated by study participants and was not associated with any serious adverse effects. Efficacy measurements in this small study indicate a possible effect in maintaining visual acuity. However, the absence of significant effects on other outcomes measures in this study suggests that OT-551, in the current concentration and mode of delivery, may have limited or no benefit as a treatment for GA ( number, NCT00306488).

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose To determine the relationship between structural parameters of the outer retina on spectral-domain optical coherence tomography (SD-OCT) and microperimetric retinal sensitivity in early stages of age-related macular degeneration (AMD). Design Prospective, observational study. Participants Seventy-five eyes of 75 participants with early stages of AMD (drusen ≥125 μm, with/without pigmentary abnormalities) and 25 control participants of a similar age. Methods Participants underwent microperimetry testing and high-resolution SD-OCT scans. Structural parameters at 5 central points (0°, 1°, and 2.33° nasal and temporal to the fovea along the horizontal axis) corresponding to areas tested by microperimetry were compared. Structural parameters included outer segment (OS) length, thickness and elevation of the retinal pigment epithelium (RPE) band, grading of the inner-segment ellipsoid (ISe) band integrity, and presence of hyperreflective foci (HF). Main Outcome Measures Relationship between structural parameters and retinal sensitivity. Results Retinal sensitivity was significantly correlated with RPE elevation (P < 0.001), ISe grading (P < 0.001), and presence of HF (P ≤ 0.018) at all test points, but not with OS length (P ≥ 0.093) or RPE thickness (P ≥ 0.125). However, multiple linear regression analyses revealed that only ISe grading (P ≤ 0.011) and RPE elevation (P ≤ 0.030) remained significantly associated with retinal sensitivity at all points. By using a simple linear model incorporating ISe grading and RPE elevation to predict values of retinal sensitivity, the 95% limits of agreement between the predicted and the actual value was ±3.83 dB. Conclusions The integrity of the ISe band and drusen-associated RPE elevation are significant independent predictors of microperimetric retinal sensitivity. Our findings imply that these 2 structural parameters may be surrogate markers of retinal function in the early stages of AMD.
    Ophthalmology 07/2014; · 5.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need.
    Intractable & rare diseases research. 08/2012; 1(3):103-14.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The molecular pathways contributing to visual signal transduction in the retina generate a high energy demand that has functional and structural consequences such as vascularization and high metabolic rates contributing to oxidative stress. Multiple signaling cascades are involved to actively regulate the redox state of the retina. Age-related processes increase the oxidative load, resulting in chronically elevated levels of oxidative stress and reactive oxygen species, which in the retina ultimately result in pathologies such as glaucoma or age-related macular degeneration, as well as the neuropathic complications of diabetes in the eye. Specifically, oxidative stress results in deleterious changes to the retina through dysregulation of its intracellular physiology, ultimately leading to neurodegenerative and potentially also vascular dysfunction. Herein we will review the evidence for oxidative stress-induced contributions to each of the three major ocular pathologies, glaucoma, age-related macular degeneration, and diabetic retinopathy. The premise for neuroprotective strategies for these ocular disorders will be discussed in the context of recent clinical and preclinical research pursuing novel therapy development approaches.
    International Journal of Molecular Sciences 01/2014; 15(2):1865-86. · 2.46 Impact Factor

Full-text (2 Sources)

Available from
May 15, 2014